Several animal models exist to study the role of synaptic receptors in stress and anxiety associated with alcohol abuse. These models will be used by the investigators of this Integrated Neuroscience Initiative on Alcoholism (IMA). Unfortunately, some models of great interest demonstrate perinatal lethality and cannot be used to study the effect of receptor deletion on alcohol related phenotypes. This is the case of the NR2B subunit of the NNIDA receptor which once deleted results in mice dying soon after birth. Furthermore, other models of interest are not currently available to the MA investigators and thus need to be created. The goals of this Gene-Targeted Mouse Core are to 1) create new animal models using the cre-lox system to allow for inducibility of gene deletion and 2) provide simple PCR protocols for genotyping of these animals. These animal models will be made available immediately to all MA investigators, and after initial characterization to other investigators in related fields. The core will also maintain during the entire funding period a minimal colony (breeding pairs) of each line (new and existing) for distribution to INIA investigators. The Core takes advantage of a very successful collaboration between the Delpire lab, which has generated several models of cation-chloride cotransporter knockouts, and the existing Vanderbilt University Ingram Cancer Center Transgenic/ES cell Core, which has extensive experience in aN aspects of gene targeting and manipulation of mouse embryos.